Challenges and Opportunities in Cancer Drug Resistance.

Chemical Reviews
Richard A WardPaul D Smith

Abstract

There has been huge progress in the discovery of targeted cancer therapies in recent years. However, even for the most successful and impactful cancer drugs which have been approved, both innate and acquired mechanisms of resistance are commonplace. These emerging mechanisms of resistance have been studied intensively, which has enabled drug discovery scientists to learn how it may be possible to overcome such resistance in subsequent generations of treatments. In some cases, novel drug candidates have been able to supersede previously approved agents; in other cases they have been used sequentially or in combinations with existing treatments. This review summarizes the current field in terms of the challenges and opportunities that cancer resistance presents to drug discovery scientists, with a focus on small molecule therapeutics. As part of this review, common themes and approaches have been identified which have been utilized to successfully target emerging mechanisms of resistance. This includes the increase in target potency and selectivity, alternative chemical scaffolds, change of mechanism of action (covalents, PROTACs), increases in blood-brain barrier permeability (BBBP), and the targeting of allosteric pockets. Fina...Continue Reading

References

Sep 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·A E Wakeling, J Bowler
Dec 9, 1982·Nature·S PulcianiM Barbacid
Jan 1, 1982·Medical and Pediatric Oncology·R L Momparler
Dec 3, 1999·The International Journal of Biochemistry & Cell Biology·D Linnekin
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Jun 1, 1997·The Australasian Journal of Dermatology·B K ArmstrongD R English
Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
Jul 27, 2001·Current Pharmaceutical Biotechnology·A J Grillo-LópezJ Rosenberg
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
May 10, 2002·The American Journal of Pathology·Christopher L CorlessMichael C Heinrich
Jun 28, 2002·Cancer Cell·Douglas R Green, Gerard I Evan
Jan 17, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·P W ManleyJ Zimmermann
Mar 26, 2003·Seminars in Cancer Biology·Boris Zhivotovsky, Sten Orrenius
Mar 30, 1957·Nature·C HEIDELBERGERJ SCHEINER
Sep 30, 1950·British Medical Journal·R DOLL, A B HILL
Dec 29, 2004·International Journal of Pharmaceutics·Qing WangIsmael J Hidalgo
Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
Mar 10, 2005·The Journal of Experimental Medicine
Nov 8, 2005·Nature·David B SolitNeal Rosen
Dec 27, 2005·Gene·Nicola NormannoDavid S Salomon
Jan 18, 2006·Nature Chemical Biology·Francisco J AdriánNathanael S Gray
Jun 24, 2006·The Oncologist·Kadri Altundag, Nuhad K Ibrahim
Nov 7, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marissa N BalakWilliam Pao
Dec 13, 2006·ChemMedChem·Zhengying PanJames T Palmer
Dec 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Simona SoveriniUNKNOWN GIMEMA Working Party on Chronic Myeloid Leukemia
Feb 24, 2007·Nature Reviews. Cancer·Sreenath V SharmaDaniel A Haber
Mar 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Vicki L GoodmanRichard Pazdur
Mar 6, 2007·Nature Chemical Biology·Jimmy A BlairKevan M Shokat
May 15, 2007·Oncogene·A S DhillonW Kolch
Feb 14, 1896·Science·W C Röntgen
Jan 4, 1957·Science
Nov 3, 2007·The Lancet Oncology·Jane F Apperley
Nov 20, 1948·Nature·G A R KON, W C J ROSS
Jan 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cai-Hong YunMichael J Eck
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·James TsaiGideon Bollag

❮ Previous
Next ❯

Citations

Dec 22, 2020·Chemical Society Reviews·Bethany M CooperDavid R Spring
Jan 14, 2021·Cell Chemical Biology·Ruth NussinovVadim Gaponenko
Mar 21, 2021·Molecular Cancer·Parvez KhanMohd Wasim Nasser
May 8, 2021·Future Medicinal Chemistry·Fabian Fischer, Leandro A Alves Avelar
Jul 3, 2021·Antioxidants·Kenji M FujiharaNicholas J Clemons
Jul 20, 2021·Frontiers in Chemistry·Fei YuJihong Zhang
Jul 29, 2021·ELife·Ioannis GaldadasFrancesco Luigi Gervasio
Oct 7, 2021·Advanced Materials·Kenward JungCyrille Boyer
Nov 3, 2021·Nano Convergence·Jessica A Kemp, Young Jik Kwon

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Antibody Engineering

Antibody engineering technologies are constantly advancing to improve the clinical effectiveness of monoclonal and bispecific antibodies. Discover the latest research on Antibody Engineering here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Related Papers

Molecular Cancer Therapeutics
Frank LoganzoHans-Peter Gerber
Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Orit LaviDoron Levy
Cancers
Lucía Gandullo-SánchezAtanasio Pandiella
© 2021 Meta ULC. All rights reserved